In this revised R01 application, we are requesting 5 years of support to randomized controlled comparative effectiveness trial (RCT) to test the relative efficacy and cost-effectiveness of an adapted, brief, version of an evidence-based intervention (EBI) vs. the original EBI targeting HIV+ drug users. Through the CDC's Diffusion of Effective Behavioral Interventions (DEBI) program, a number of evidence-based HIV prevention approaches are now widely available for use with people living with HIV/AIDS (PLWA). The substantial resources required for training, implementation, monitoring, and evaluation of current EBIs targeting HIV+ DUs, however, reduces the likelihood that these EBIs can be properly adopted and sustained in clinical settings (e.g., drug treatment programs, HIV clinical care, etc.) Moreover, the uptake of EBIs applicable to HIV+ DUs has been quite limited and the number of new annual HIV infections - a significant portion of which are directly and indirectly attributable to HIV+ DUs - has remained ~56,300 in the U.S. Thus, HIV+ DUs remain an important priority population since only HIV+ persons can new transmit infections and because DUs continue to contribute greatly to the persistent HIV epidemic in the U.S. via drug- and sex-related HIV risk behaviors that are entirely preventable through properly tailored, and strategically placed, interventions that are efficacious cost-effective, and sustainable in clinical settings. NIDA has recognized this translational gap and has provided funding for our team of investigators to adapt and optimize EBI approaches for implementation among priority populations in drug treatment and correctional settings. Our formative research in drug treatment settings has resulted in 3H+ - an empirically adapted, substantially abbreviated version of HHRP+, an EBI targeting HIV+ DUs. We are now positioned to conduct a randomized trial comparing the relative efficacy and cost-effectiveness of the brief EBI (3H+) vs. the original EBI (HHRP+). Our specific aims are: Specific Aim 1: Using a non-inferiority analytical approach, test whether 3H+ is comparable (i.e., within a 10% margin) to the original HHRP+ in reducing HIV risk behaviors and improving ART adherence in a randomized controlled comparative effectiveness trial among 256 HIV+ persons in drug treatment who report unsafe injection drug use practices or sexual risk behavior, and Specific Aim 2: Using results from specific aim 1, conduct a cost-effectiveness analysis of the two interventions in terms of preventing HIV transmission and improving quality of life. Findings will be used to empirically inform the allocation of prevention resources. This will be the first tial to test the relative efficacy and cost effectiveness of an adapted, brief, version of an EBI vs. an original EBI targeting HIV+ DUs, and thus provides an innovative approach to move the field forward. Moreover, if confirmed to be as efficacious, more cost-effective, and more easily implemented, the 3H+ intervention could be rapidly disseminated for implementation as part of routine care within common drug treatment programs - a true integration of HIV prevention science and drug treatment services. PUBLIC HEALTH RELEVANCE: A randomized controlled comparative effectiveness trial (RCT) will be used to evaluate the efficacy and cost- effectiveness of an adapted, brief, version of an evidence-based intervention (EBI) called Holistic Health for HIV (3H+) vs. the original EBI -- Holistic Health Recovery Program for HIV+s (HHRP+) targeting HIV+ drug users (DUs) in the context of a community-based drug treatment setting. If confirmed to be as efficacious, more cost-effective, and more easily implemented, the 3H+ intervention could be rapidly disseminated for implementation as part of routine care within common drug treatment programs - a true integration of HIV prevention science and drug treatment services. 1